EVA WIDERSTRÖM-NOGA, D.D.S., PH.D.

SCI-related Neuropathic Pain Phenotypes and Biomarkers

Research Interests

Back ground: Chronic pain is a serious consequence of SCI that can be both persistent and severe and cause significant psychosocial impact and a substantially reduced quality of life. Neuropathic pain associated with SCI is not consistently relieved by currently available treatments and even the best pharmacological interventions require high numbers needed to treat. Indeed, pain relief, together with issues related to occupational and sexual activities, has been identified as significant and unmet needs after SCI. The refractory nature of pain following SCI and the associated psychosocial burden emphasize the need for a greater understanding of not only the role of pathophysiological but also psychosocial factors. While basic research has identified multiple underlying mechanisms of neuropathic pain and designed interventions to target them, significant knowledge gaps exist regarding the best methods to characterize pain phenotypes and their relationship to the underlying pain mechanisms and psychosocial impact. Because neuropathic pain is dependent on multiple mechanisms, this knowledge gap is a significant barrier to successful management of neuropathic pain.

My research program is focused on the identification of clinical correlates of underlying mechanisms of neuropathic pain after neurological injury in order to facilitate translation of basic research findings and the development of tailored clinical interventions. My research focus is interdisciplinary and involves extensive multimodal pain evaluations of pain symptoms and its psychosocial impact, quantitative assessment of neurological function, and biomarkers including non-invasive brain imaging, and genetic analysis.

Pain phenotypes: A recent analysis of pain history data from 156 persons with SCI and neuropathic pain revealed three distinct symptom profiles: (1) aching, throbbing pain, exacerbated by cold weather and constipation; (2) stabbing, penetrating, and constant pain of high intensity; and (3) burning, electric, and stinging pain aggravated by mechanical stimuli such as touch and muscle spasms. The neuropathic pain symptom subgroups were significantly associated with greater psychosocial distress. These findings provide support for the presence of specific pain symptom patterns or “profiles” after SCI that are associated with psychosocial factors. We have also shown that specific neuropathic pain phenotypes are perceived as particularly disturbing and predictive of using prescription medication.

Sensory signs: Understanding the relationship between sensory abnormalities and the neuropathic pain is critical if these measures are to be used to further the diagnosis of neuropathic pain and provide links to specific pain mechanisms. Previous results from our laboratory suggest that neuropathic pain is commonly exacerbated by multiple innocuous factors, situations, and behaviors. We also found that greater extent of sensory abnormalities was not only significantly associated with neuropathic pain but also with greater psychosocial impact. Similarly, recent data from our lab supported the reliability and validity of quantitative sensory testing (QST) in the SCI chronic pain population. Our data suggest that the use of QST is an important tool for defining pain phenotypes.

Brain imaging: Neuroimaging suggest that pain perception is dependent on a network of sensory cortical areas, limbic areas, associative cortex and subcortical structures, such as the thalamus. Dysfunction in these networks may underlie the generation and maintenance of chronic pain and associated conditions. Magnetic Resonance Spectroscopy (MRS) is a non-invasive method to assess brain chemistry. MRS can determine the distribution and concentration of naturally occurring molecules such as N-acetyl aspartate (NAA), one of the most common amino acids of the brain. In a previous study MRS was used to assess metabolic activity in the thalamus, in people with SCI and chronic pain. Severity of pain was significantly correlated with low NAA and high Ins concentrations. The low levels of NAA were hypothesized to be related to a decreased function of inhibitory neurons in the thalamic region, whereas higher concentrations of Ins were hypothesized to reflect gliosis. We are currently conducting imaging studies to assess neuronal function in the thalamus and areas of the cingulate cortex in individuals with neuropathic pain and SCI.